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Innate Immune Agonists in Cancer Immunotherapy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 4121

Special Issue Editor


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Guest Editor
Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
Interests: medicinal chemistry; immunotherapy; innate immunity; pattern recognition receptors; NOD-like receptors

Special Issue Information

Dear Colleagues,

There is a pressing need to overcome the low immunogenicity of cancer vaccines as well as to lower the tumor microenvironment’s tolerance. Pathogen-associated molecular patterns (PAMPs) delivered into tumors make them look like pathogen-infected tissues and elicit an innate immune activation cascade to lower this tolerance. Our immune cells contain a series of pattern recognition receptors (PRRs), activated by PAMPs as well as small molecule innate immune agonists, which structurally resemble PAMPs but lack their infectious capacities. These agonists engage the immune cells via the induction of inflammatory cytokines, interferons, and co-stimulatory molecules and provide indispensable initial signals that determine the type, magnitude, and durability of the immune response. Several small molecule PRR agonists have been developed and actively pursued for their antitumor potential, either as immunotherapeutics or vaccine adjuvants. This Special Issue aims to highlight the use of innate immune agonists in cancer immunotherapy as an approach that has enormous, yet somehow still untapped, potential to induce antitumor immunity.

Dr. Žiga Jakopin
Guest Editor

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Keywords

  • NOD agonists
  • TLR agonists
  • STING agonists
  • RIG-I agonists
  • CLR agonists
  • pattern recognition receptors
  • cancer immunotherapy
  • antitumor
  • innate immune agonists
  • immunostimulants

Published Papers (1 paper)

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Research

13 pages, 2095 KiB  
Article
Resveratrol Activates Natural Killer Cells through Akt- and mTORC2-Mediated c-Myb Upregulation
by Yoo-Jin Lee and Jongsun Kim
Int. J. Mol. Sci. 2020, 21(24), 9575; https://doi.org/10.3390/ijms21249575 - 16 Dec 2020
Cited by 17 | Viewed by 3592
Abstract
Natural killer (NK) cells are suitable targets for cancer immunotherapy owing to their potent cytotoxic activity. To maximize the therapeutic efficacy of cancer immunotherapy, adjuvants need to be identified. Resveratrol is a well-studied polyphenol with various potential health benefits, including antitumor effects. We [...] Read more.
Natural killer (NK) cells are suitable targets for cancer immunotherapy owing to their potent cytotoxic activity. To maximize the therapeutic efficacy of cancer immunotherapy, adjuvants need to be identified. Resveratrol is a well-studied polyphenol with various potential health benefits, including antitumor effects. We previously found that resveratrol is an NK cell booster, suggesting that it can serve as an adjuvant for cancer immunotherapy. However, the molecular mechanism underlying the activation of NK cells by resveratrol remains unclear. The present study aimed to determine this mechanism. To this end, we investigated relevant pathways in NK cells using Western blot, real-time polymerase chain reaction, pathway inhibitor, protein/DNA array, and cytotoxicity analyses. We confirmed the synergistic effects of resveratrol and interleukin (IL)-2 on enhancing the cytolytic activity of NK cells. Resveratrol activated Akt by regulating Mammalian Target of Rapamycin (mTOR) Complex 2 (mTORC2) via phosphatase and tensin homolog (PTEN) and ribosomal protein S6 kinase beta-1 (S6K1). Moreover, resveratrol-mediated NK cell activation was more dependent on the mTOR pathway than the Akt pathway. Importantly, resveratrol increased the expression of c-Myb, a downstream transcription factor of Akt and mTORC2. Moreover, c-Myb was essential for resveratrol-induced NK cell activation in combination with IL-2. Our results demonstrate that resveratrol activates NK cells through Akt- and mTORC2-mediated c-Myb upregulation. Full article
(This article belongs to the Special Issue Innate Immune Agonists in Cancer Immunotherapy)
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